1. Field of the Invention
The invention relates to a process for the preparation of 2,5-disubstituted pyridines by reaction of enamines with .beta.-amino-acrylonitriles, followed by cyclisation of the open-chain intermediate with protic acids or ammonia.
2,5-Disubstituted pyridines are important intermediates for the preparation of herbicides (EP 108,483), insecticides (EP 235,725) and pharmaceuticals (CA 1,189,509, which is equivalent to DE-OS (German Published 2,812,585 and DE-OS (German Published Specification) 2,812,586).
2. Description of the Related Art
The required 2,5-disubstituted pyridines can be obtained either by ring-closure reactions or by substitution of 3-alkyl-pyridines. However, the latter synthesis involves unavoidable formation of positional isomers.
An interesting approach is the joining together into a ring of morpholinopropene and acrylic acid derivatives, that is a reaction of C.sub.2 and C.sub.3 building blocks. However, the dihydropyridines obtainable by this reaction have to be aromatised by a complicated procedure (EP 108,483). The use of .alpha.-chloro-acrylonitrile (EP 162,464) leads directly to 2-chloro-5-methyl-pyridine in low yield.
The reaction of C.sub.4 - and higher enamines with .alpha.-chloroacrylonitrile is described in Tetrahedron 24 (1968), 3369. However, it is plain that secondary reactions are taking place; a satisfactory yield is obtainable only at very low temperatures, which are expensive to achieve under industrial conditions (Synthesis 1985, 1116). Considering these references, it was therefore surprising that the open-chain intermediates of 4-R.sup.1 -5-amino-penta-2,4-dienonitriles, which can be cyclised to give the corresponding 2,5-disubstituted pyridines, are obtainable in a simple manner by using .beta.-aminoacrylonitriles.